Tumor-specific delivery of a paclitaxel-loading HSA-haemin nanoparticle for cancer treatment

A cancer-targeted chemotherapy could potentially eradicate cancers if anticancer drugs are delivered precisely to the cancers. Although various types of nanoparticles have been developed for cancer-specific delivery of anticancer drugs, the drug delivery capabilities of these nanoparticles were not specific enough to eradicate cancer. Here, we developed a targeting-enhancing nanoparticle of paclitaxel, in which paclitaxel was encapsulated with a human serum albumin-haemin complex through non-covalent bonding. The average diameter of TENPA was approximately 140 nm with a zeta potential of +29 mV. TENPA maintained its structural integrity and stability without forming protein coronas in the blood for optimal passive targeting. These characteristics of TENPA resulted in paclitaxel accumulation that was 4.1 times greater than that of Abraxane, an albumin-bound paclitaxel, in cancer tissue. The dramatic improvement in cancer targeting of TENPA led to reduced systemic toxicity of paclitaxel and eradication of end-stage cancer in a xenografted mouse experiment. We developed a new concept of nanoparticle, TENPA, an encapsulated paclitaxel with albumin. To formulate TENPA, albumin is non-covalently polymerized using hemin as an adhesive agent for nanoformulation. The noncovalent albumin-hemin complex forms a very stable nanoparticle so that TENPA maintains its structural integrity and stability without forming protein corona in blood for optimal passive targeting. At the same time, albumin-hemin complex composing the shell of TENPA functioned as active targeting moieties respectively. These characteristics of TENPA contribute to reduction of toxicity and enhancement of efficacy, successfully demonstrating complete eradication of even late-stage cancer in a xenografted mouse experiment. [Display omitted]